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While microcredits are, by the development practitioners, repeatedly hailed as a useful measure of development policy, this empirical research in Bangladesh arrives at different results: the governing and disciplinary measures are necessary to trigger the best possible repayment success. Based on interviews with the microfinance beneficiaries, loan officers, and microfinance experts in Bangladesh, I chart some of the most frequently used governing and disciplinary techniques including fictitious proximity of loan officers, their fields of visibility and surveillance processes. The “success” of credit delivery is a neoliberal stance that ensures the ceaseless debt repayment process using the intentional and planned conduct, capitalizing social capital and credit honour reputation, surveillance over business enterprises, use of equivocal language and different forms of deception. The development strategy through microfinance in Bangladesh is a development “dispositif” with a changing shift in its declared social missions.

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Strip-mined land (SML) disturbed by coal-mining is the non-crop land resource that can be utilized to cultivate high-yielding energy crops such as miscanthus for bioenergy applications. However, the biomass yield potential, annual availability and environmental impacts on growing energy crops in SML are less understood. In this study, we estimated the yield potential of miscanthus (Miscanthus sinensis) in SML and its environmental impacts on local streams using the Soil and Water Assessment Tool (SWAT). After calibration and validation of the SWAT model, the results demonstrated that miscanthus yield potentials were 2.6 (0.8−5.53), 10.0 (1.3−16.0) and 16.0 (1.34−26.0) Mg ha-1 with the fertilizer application rate of 0, 100, and 200 kg-N ha-1 respectively. Furthermore, cultivation of miscanthus in the SML has the potential to reduce sediment (~20%) and nitrate (2.5%−10.0 %) loads reaching to water streams with a marginal increase in phosphorus load. The available SML in the United States could produce about 10 to 16 dry Tg of biomass per year without negatively impacting the water quality. In conclusion, SML can provide a unique opportunity to produce biomass for bioenergy applications, while improving stream water quality in highly dense mining area (the Appalachian region) in the United States.

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This paper presents a methodology for the generation of a limited and representative number of water demand scenarios, taking into account the natural variability and spatial correlation of nodal consumption in a Water Distribution Network (WDN), and estimates their corresponding occurrence probabilities. Scaling laws are used to evaluate the statistics of water consumption at each node as a function of the number of users, considering the main statistical features of the unitary user's demand. Besides, consumption at each node is considered to follow a Gamma probability distribution. A high number of groups of cross-correlated demands, i.e. scenarios, for the entire network were generated using Latin Hypercube Sampling (LHS) and the numerical procedure proposed by Iman and Conover. The Kantorovich distance is used to reduce the number of scenarios and estimate their corresponding probabilities, while keeping the statistical information on nodal consumptions. By hydraulic simulation, the whole number of generated demand scenarios was used to obtain a corresponding number of pressure scenarios on which the same reduction procedure was applied. The probabilities of the reduced scenarios of pressure were compared with the corresponding probabilities of demand.

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Quantitative trait loci (QTL) are genomic regions associated with phenotype variation of quantitative traits in a population. To date, a total of 267 QTL for 29 quantitative traits have been reported in 13 studies on flax. Of these, 200 QTL from 12 studies were identified based on genetic maps, scaffold sequences, or pre-released chromosome-scale pseudomolecules. Molecular markers for QTL identification differed across studies but were mainly based on simple sequence repeat (SSR) or single nucleotide polymorphism (SNP) markers. This article provides methods with software tools and database files to uniquely map SSR and SNP markers from different references onto the recently released chromosome-scale pseudomolecules. Using these methods, 195 QTL were successfully sorted onto the 15 flax chromosomes and grouped into 133 co-located QTL clusters. Mapping of QTL from different studies to the same reference enables comparisons and facilitates genome-wide QTL analysis, candidate gene scanning, and breeding applications.

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The Bullying in Sicilian School study aimed to investigate the prevalence of bullying and the short-term effects on the students’ perception of bullying after a preventive intervention conducted among teachers of first-grade secondary schools of Palermo, Sicily (Italy). Between the 2017/2018 and 2018/2019 school years, a pre-post intervention study was conducted among ten schools sampled and categorized by neighbourhood socio-economic index. A questionnaire investigating physical, verbal and indirect bullying, observers role, prosociality and resiliency in bullying phenomena was administered before and after a formative cascade-training intervention on teachers of the selected classes. 428 students participated the study (70.8% response rate). A decrease in the bullying episodes after the intervention carried out was reported by students in all areas explored. The verbal bullying was the one that demonstrated the most significant decrease, together with physical bullying and observer area. In particular, a statistically significant decrease was reported for students of schools with an intermediate socioeconomic level. The encouraging results obtained in reducing bullying episodes, together with its low cost of human and economic resources, could suggest the research extension on a regional/national scale.

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A combination of physical-chemical analysis has been used to monitor the aging of red wines from D.O. Toro (Spain). The changes in the chemical composition of wines that occur along aging time can be permitted to discriminate wine samples collected after one, four, seven and ten months of aging. Different computational models were used to develop a good authenticity tool to certificate wines. In this research different models have developed: Artificial Neural Network models (ANNs), Support Vector Machine (SVM) and Random Forest (RF) models. The results obtained for the ANN model developed with sigmoidal function in the output neuron and the RF model permit to determine the aging time, with an average absolute percentage deviation below 1% and it can conclude that these two models have demonstrated its capacity as a valid tool to predict the wine age.

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The present study is the second step (concerning the normal-diet restoration) of the our previous one (concerning the calcium-free diet) to determine whether the normal-diet restoration, with/without concomitant PTH(1-34) administration, can influence amounts and deposition sites of the total bone mass. Histomorphometric evaluations and immunohistochemical analysis for Sclerostin expression were conducted on the vertebral bodies and femurs in rat model. The final goals are: i) to define timing and manners of bone mass changes when calcium is restored in the diet; ii) to analyze the different involvement of the two bony architectures having different metabolism (i.e. trabecular versus cortical bone); iii) to verify the eventual role of PTH(1-34) administration. Results evidenced the greater involvement of the trabecular bone with respect to the cortical one, in answering to different calcium diet content, and the effect of PTH mostly in the recovery of trabecular bony architecture. The main findings emerged from the present study are: i) the importance of the interplay between mineral homeostasis and skeletal homeostasis in modulating and guiding bone answers to dietary/metabolic alterations and ii) the evidence that the more involved bony architecture is the trabecular one, the most susceptible to the dynamical balance of the two homeostases.

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Groundwater plays a pivotal role as the largest potable water sources in Bangladesh. However, the quality of the groundwater faces challenges due to xenobiotic compounds in it. Excess amount of arsenic (As) has already been found in groundwater in many parts of Bangladesh. Thus, this study was conducted to assess the water quality and associated human health risk in central Bangladesh. A total of 99 groundwater samples from the central part of Bangladesh were analyzed to assess human health risk due to high level of nitrate (NO3-) and other trace elements i.e. arsenic (As), iron (Fe), and manganese (Mn). It was found that NO3- concentration (253.17 mg/L) in the groundwater samples exceeds the recommended guideline value by the WHO (50 mg/L). Moreover, this study area also characterized with elevated concentration of As (19.44 µg/L), Fe (811.35 µg/L), and Mn (455.18 µg/L) in the groundwater. Non-carcinogenic human health risk was calculated by justifying HQ (Hazard Quotient) and HI (Hazard Index) and attributed potential conjunctive human health risks due to NO3-, As, Fe and Mn in the study area. Moreover, high carcinogenic risk was found due to As contamination in the groundwater samples in the study area.

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Delineating the cropping area of cocoa agroforests is a major challenge for quantifying the contribution of the land use expansion to tropical deforestation. Discriminating cocoa agroforests from tropical transition forests using multi-spectral optical images is difficult due to a similarity in the spectral characteristics of their canopy; moreover, optical sensors are largely impeded by the frequent cloud cover in the tropics. This study explores multi-season Sentinel-1 C-band SAR image to discriminate cocoa agroforests from transition forests for a heterogeneous landscape in central Cameroon. We use an ensemble classifier, random forest, to average SAR image texture features of GLCM (Grey Level Co-occurrence Matrix) across seasons; next, we compare classification performance with results from RapidEye optical data. Moreover, we assess the performance of GLCM texture feature extraction at four different grey level quantization: 32bits, 8bits, 6bits, and 4bits. The classification overall accuracy (OA) of texture-based maps outperformed that from an optical image; the highest OA of 88.8% was recorded at 6bits grey level. This quantization level, in comparison to the initial 32bits in SAR images, reduced the class prediction error by 2.9%. Although this prediction gain may be large for the landscape area, the resultant thematic map reveals the decrease and fragmentation of forest cover by cocoa agroforests. According to our classification validation, the Shannon entropy (H) or uncertainty provides a reliable validation for class predictions and reveals detail inference for discriminating inherently heterogeneous vegetation categories. The texture-based classification achieved a reliable accuracy considering the heterogeneity of the landscape and vegetation classes.

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Background: Despite the abundant scientific literature on entrepreneurship, there is still only limited information on young students’ entrepreneurial intentions. The reasons may be generally found in the different conceptual approaches to entrepreneurial intention and particularly in the variables that regulate and act as antecedents to such intentions. This bias has generated different lines of investigation into the factors relating to entrepreneurial intention among students: one is centered on the variables that influence entrepreneurial intention, in particular, relational, educational, and psychological variables; and the other is centered on the antecedents of entrepreneurial intention, among which is entrepreneurial interest. Methods: In the present paper, we seek to analyze the relationship between the entrepreneurial interest of Spanish youth and a set of socio-educational, psychological, and health-related variables using principal component analysis. A previously validated ad hoc questionnaire was administered to 1764 students (15–18 years old). Results: Notably, few Spanish youth expressed significantly high entrepreneurial interest; those who did were mostly men with a family tradition of entrepreneurial parents, who held high perceptions of their health and quality of life and considered it important in business to detect opportunities beforehand and to create employment. Conclusions: Their principal motives were to improve their professional development, to put their ideas into practice, and to achieve economic independence. This paper proposes the early detection of entrepreneurial interests in young people in order to reinforce these interests as potential long-term initiatives.

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Background: Increased DNA damage and the propension to cancer development, depend on the modulation of the mechanisms to control and maintain genomic integrity. Poly(ADP-Ribose)Polymerase activation and automodification are early responses to genotoxic stress. Upon binding to DNA strand breaks, the enzyme, a molecular DNA nick sensor, is hyperactivated: this is the first step in a series of events leading to either DNA repair or apoptosis. Enzyme hyperactivation and automodification can be easily measured and are widely used to look at DNA damage extent in the cell. We investigated whether these two markers (increased catalytic activity and auto modification), could help to monitor DNA damage in lymphocytes of flower growers from Southern Italy, occupationally exposed to pesticides. Methods: Peripheral lymphocyte lysates were analysed for Poly(ADP-Ribose) Polymerase activity, and by SDS-PAGE and anti-Poly(ADP-Ribose)Polymerase 1-antibody to measure automodified anti-Poly(ADP-Ribose) Polymerase levels by densitometry. Results: Poly(ADP-Ribose)Polymerase activity levels were consistent with those of enzyme auto-modification. Growers daily exposed to pesticides, showed both biomarkers very high, either in the presence or in the absence of pathologies. Conclusions: PARP activity and auto-modification in peripheral blood lymphocytes are possible,non-invasive, and routinar tools to monitor the healthy conditions of floricoltorists.

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In this work a new pre-tuning multivariable PID controllers method for quadrotors is put forward. A procedure based on LQR/LQG theory is proposed for attitude and altitude control. With the aim of analyzing performance and robustness of the proposed method, a non-linear mathematical model of the DJI-F450 quadrotor is employed, where rotors dynamics, togheter with sensors drift/bias properties and noise characteristics of low-cost comercial sensors typically used in this type of applications (such as MARG with MEMS technology and LIDAR) are considered. In order to estimate the state vector and compensate bias/drift effects on rate gyros of the MARG, a combination of filtering and data fusion algorithms (Kalman filter and Madgwick algorithm for attitude estimation) are proposed and implemented. Performance and robutsness analysis of the control system is carried out by means of numerical simulations, which take into account the presence of uncertainty in the plant model and external disturbances. The obtained results show that the proposed pre-tuning method for multivariable PID controller is robust with respect to: a) parametric uncertainty in the plant model, b) disturbances acting at the plant input, c) sensors measurement and estimation errors.

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Abstract: The Inconel 625 is a nickel-based alloy has been widely used in the high-temperature application. The Inconel 625 exhibits unstable plastic flow at elevated temperature characterized by serrated yielding, known as Portevin-Le Chatelier effect. The aim of this work is to evaluate the mechanical properties at high temperatures of the Inconel 625. The tensile tests were performed in the temperature range of room temperature until 1000 °C and strain rate of 2x10^-4 to 2x10^-3 s^-1. The creep tests were performed in the temperature range of 600-700 °C, in the stress range of 500-600 MPa in a constant load mode. The surface fracture was observed by optical and scanning electron microscopy. Serrated stress-strain behavior was observed in the curves obtained at 200 to 700 °C, which was associated with the dynamic strain aging effect. The yield strength and the elongation values show an anomalous behavior as a function of the test temperature. An intergranular cracking was observed specimen tensile tested at 500 °C that can be attributed to the decohesion of the carbides along the grain boundaries. The fracture surface of the specimen tensile tested at 700 °C showed the predominance of transgranular cracking with tear dimples with a parabolic shape.

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Background: Identification of cancer biomarkers that are differentially expressed (DE) under two biological conditions is an important task in many microarray studies. There exist several methods in the literature in this regards and most of these methods designed especially for unpaired samples, which does not satisfy the requirements of paired samples where the gene expressions are taken from the same patients before and after treatment. Furthermore, the traditional biomarker identification methods based on either p-values or fold change (FC) values. However, sometimes, p-value based results do not comply with FC based results due to the smaller variance of gene expressions. There are some methods that combine both p-values and FC values to solve this problem. But, these methods also show weak performance for small-sample case in presence of outlying expressions. To overcome this problem, in this paper an attempt is made to develop a hybrid robust SAM-FC approach by combining rank of FC values and rank of p-values based on SAM statistic using minimum β-divergence method, which is designed for paired samples. This method introduces a weight function known as β-weight function. This weight function produces larger weights corresponding to usual/normal expressions and smaller weights for unusual/outlying expressions. The β-weight function plays the significant role on the performance of the proposed method. Results: The proposed method uses β-weight function as a measure of outlier detection by setting β=0.2. We unify both classical and robust estimates using β-weight function such that maximum likelihood estimators (MLEs) are used in absence of outliers and minimum β-divergence estimators are used in presence of outliers to obtain reasonable p-values and FC values in the proposed method. We examined the performance of proposed method in a comparison of some popular methods (t-test, SAM, LIMMA, Wilcoxon, WAD, RP and FCROS) using both simulated and real gene expression profiles for both small-and large-sample cases. From the simulation and a real spike in data analysis results we observed that the proposed method outperforms other methods for small-sample case in presence of outliers and it keeps almost equal performance with other robust methods (Wilcoxon, RP and FCROS) otherwise. From a head-and-neck cancer (HNC) dataset the proposed method identified 2 genes (CYP3A4, NOVA1) that are significantly enriched in linoleic acid metabolism, drug metabolism, steroid hormone biosynthesis and metabolic pathways. The survival analysis through Kaplan-Meier curve revealed that combined effect of these 2 genes has prognostic capability and they might be promising biomarker of HNC. Moreover, we retrieved the 12 candidate drugs based on gene interaction from glad4u and drug bank databases. Conclusion The identified drugs showed statistical significance and critical role of the proteins indicate that these proteins might be therapeutic target in cancer. Thus, elucidating the associations between the drugs identified in the present study require further investigations.

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The authors intend to establish new oscillation criteria for a class of generalized third order functional difference equation of the form \begin{equation}{\label{eq01}} \Delta_{\ell}\left(a_2(n)\left[\Delta_{\ell}\left(a_1(n)\left[\Delta_{\ell}z(n)\right]^{\beta_1}\right)\right]^{\beta_2}\right)+q(n)f(x(g(n)))=0, ~~n\geq n_0, \end{equation} where $z(n)=x(n)+p(n)x(\tau(n))$. We also present sufficient conditions for the solutions to converges to zero. Suitable examples are presented to validate our main results.

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The advancements in the study of the human sense of touch are fueling the field of haptics. This is paving the way for augmenting the sensory perception during objects palpation in tele-surgery, and reproducing the information through tactile feedback. Here, we present a novel tele-palpation apparatus that enables the user to detect nodules with various distinct stiffness buried in an ad-hoc polymeric phantom. The contact force measured by the platform was encoded using a neuromorphic model and reproduced on the index fingertip of a remote user through a haptic glove embedding a piezoelectric disk. We assessed the effectiveness of this feedback in allowing nodule identification under two experimental conditions of real-time telepresence: In Line of Sight (ILS), where the platform was placed in the visible range of a user; and the more demanding Not In Line of Sight (NILS), with the platform being 50 km apart. We found that the entailed percentage of identification was higher for stiffer inclusions with respect to the softer ones (average of 74% within the duration of the task), in both telepresence conditions evaluated. These promising results call for further exploration of tactile augmentation technology for telepresence in medical interventions.

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The recommendations of the panel of experts on the further development of the ‘High-Tech Strategy’ of the Government of the Federal Republic of Germany designate the biologization of economic processes along with digitization as the central driver of societal change. Various fields such as the 'biologization of materials research' were then defined in the 'Bio-Agenda' in order to walk the path from biology to innovation. In view of this perspective, we describe how the use of biological materials and mechanisms can lead to resource conservation, the production of intelligent materials and new technological and medical applications. Our strategy, based on research on ‘Biointerfaces in Technology and Medicine’, aims at the development of modular biohybrid systems that could be used as 'biofactories of the future' for sustainable production processes. To achieve this goal, in a first phase already known technologies have to be further refined and integrated in order to obtain and apply compartmentalized reaction systems on different length and time scales. In a second phase, the resulting functional units will be employed to develop dissipative systems useful for biomedical applications and advanced production processes. From a technical point of view, future success in creating 'something entirely new' will depend crucially on robust and complementary research capabilities. Since the close connection of engineering and life sciences at KIT provides an excellent basis for this endeavor, we consider the above perspectives to be feasible.

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Research on bidirectional human-machine interfaces will enable the smooth interaction with robotic platforms in contexts ranging from industry to tele-medicine and rescue. This paper introduces a bidirectional communication system to achieve multisensory telepresence during the gestural control of an industrial robotic arm. We complement the gesture-based control by means of a tactile-feedback strategy grounding on a spiking artificial neuron model. Force and motion from the robot are converted in neuromorphic haptic stimuli delivered on the user’s hand through a vibro-tactile glove. Untrained personnel participated in an experimental task benchmarking a pick-and-place operation. The robot end-effector was used to sequentially press six buttons, illuminated according to a random sequence, and comparing the tasks executed without and with tactile feedback. The results demonstrated the reliability of the hand tracking strategy developed for controlling the robotic arm, and the effectiveness of a neuronal spiking model for encoding hand displacement and exerted forces in order to promote a fluid embodiment of the haptic interface and control strategy. The main contribution of this paper is in presenting a robotic arm under gesture-based remote control with multisensory telepresence, demonstrating for the first time that a spiking haptic interface can be used to effectively deliver on the skin surface a sequence of stimuli emulating the neural code of the mechanoreceptors beneath.

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The adsorption of carbon dioxide on amino silanes-functionalized MCM-41 and SBA-15 materials is reported. The functionalization of mesoporous silicas was made by post-synthesis method, by impregnation of 3-aminopropyltriethoxysilane. The obtained materials were characterized by X-ray diffraction, scanning and transmission electron microscopies, nitrogen adsorption-desorption and X-ray photoelectron spectroscopy measurements. The carbon dioxide adsorption capacities for the samples were carried out under ambient pressures. The obtained results evidenced that amino-silanes with a terminal amine (–NH2) were functionalized through covalent coupling of this group on the surface of the channels in the ordered mesoporous silica, meaning that the amine is anchored on the surface of the bigger pores of the MCM-41 and SBA-15 support. For functionalized materials, the CO2 adsorption capacity of the AMCM-41 increased from 0.18 to 1.1 mmol·g−1, whereas for ASBA-15, it was from 0.6 to 1.8 mmol·g−1. The Lagergren kinetic algorithms were applied in order to validate the obtained results, evidencing the enhanced carbon dioxide adsorption capacity and stability of the functionalized ordered mesoporous molecular sieves.

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ZnO films with Ti atoms incorporated (TZO) in a wide range (0-18 at. %) have been grown by reactive co-sputtering on silicon and glass substrates. The influence of the titanium incorporation in the ZnO matrix on the structural and optical characteristics of the samples has been determined by Rutherford backscattering spectroscopy (RBS), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). The results indicate that the samples with low Ti content (< 4 at. %) exhibit the wurtzite-like structure, with the Ti+4 ions substitutionally incorporated into the ZnO structure, forming Ti-doped ZnO films. In particular, very low concentration of Ti (<0.9 at. %) leads to a significant increase of the crystallinity of the TZO samples. Higher Ti contents give rise to a progressive amorphization of the wurtzite-like structure so samples with high Ti content (≥18at. %), displays an amorphous structure indicating the XPS analysis a predominance of Ti-O-Zn mixed oxides. The energy gap, obtained from absorption spectrophotometry, increases from 3.2 eV for pure ZnO films to 3.6 eV for those with the highest Ti content. Ti incorporation in the ZnO samples below 0.9 at. % rises both, the blue (380 nm) and green (550 nm) bands of the photoluminescence (PL) emission, thereby indicating a significant improvement of PL efficiency of the samples.

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Abstract5′,8-Cyclo-2′-deoxyadenosine (cdA), in the 5′R and 5′Sdiastereomeric forms, are typical non strand-break oxidative DNA lesions, induced by hydroxyl radicals, with emerging importance as a molecular marker. These lesions are exclusively repaired by nucleotide excision repair (NER) mechanism with a low efficiency, thus readily accumulating in the genome. Poly(ADP-ribose) polymerase1 (PARP1) acts as an early responder to DNA damage and plays a key role as a nick sensor in the maintenance of the integrity of the genome by recognizing nicked DNA. So far, it was unknown whether the diastereomeric cdA lesions could induce specific PARP1 binding. Here we provide the first evidence of PARP1 to selectively recognize the diastereomeric lesions 5′S-cdA and 5′R-cdA in vitro as compared to deoxyadenosine in model DNA substrates (23-mers) by using circular dichroism,fluorescence spectroscopy, immunoblotting analysis and gel mobility shift assay. Several features of the recognition of the damaged and undamaged oligonucleotides by PARP1were characterized. Remarkably, PARP1 efficiently binds to both cdA lesions in the double stranded (ds)-oligonucleotides. In particular, PARP1 proved to bind 5′S-cdAwith a higher affinity constant for the 5'S lesion in a model of ds DNA than 5′R-cdA, showing different recognition patterns, also compared with undamaged dA. This new finding highlights the ability of PARP1 to recognize and differentiate the distorted DNA backbone in a biomimetic system caused by different diastereomeric forms of a cdA lesion.

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This paper analyses the evolution of the internal damage in two types of steel that show different fracture behaviours, with one of them being the initial material used for manufacturing prestressing steel wires, which shows a flat fracture surface perpendicular to the loading direction, and the other one being a standard steel used in reinforced concrete structures, which shows the typical cup-cone surface. 3mm-diameter cylindrical specimens are tested with a tensile test carried out in several loading stages and, after each of them, unloaded and analysed with X-ray tomography, which allows detection of internal damage throughout the tensile test. In the steel used for reinforcement, damage is developed progressively in the whole specimen, as predicted by Gurson-type models, while in the steel used for manufacturing prestressing steel-wire damage is developed only in the very last part of the test. In addition to the experimental study, a numerical analysis is carried out by means of the finite element method by using a Gurson model to reproduce the material behaviour.

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Chitosan decorated copper nanoparticles (CS/CuNPs) catalysts were synthesized via reduction methods utilizing green protocol. The CS/CuNPs hybrid catalysts were tested for the synthesis of quinoline derivatives utilizing one-pot multicomponent reaction (MCR) under ultrasonic irradiation. The best catalyst (CS/CuNPs) that provided good conversion reaction yield and high turnover frequency (TOF) was characterized using Fourier transform infrared (FTIR), Thermogravimetric analyses (TGA), X-ray diffraction (XRD), , scanning electron microscopy (SEM), transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS) techniques. Generalization of the scope of the proposed catalytic process was studied using different aldehydes. Excellent products yield and high TOF in even shorter reaction time (~5 min) was attained. Recyclability performance of the catalyst over five times re-use without detectable loss in product yield was recorded. The current method is green process utilizing environmentally benign catalyst and considered to be promising sustainable protocol for the synthesis of fine chemicals.

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Among the most important variables in the design of falling film microreactors (FFMRs) is the liquid film thickness as well as the gas/liquid interfacial area, which dictate the mass and heat transfer rates. In a previous work conducted in our lab the characteristics of a free-falling Newtonian liquid film have been studied and appropriate correlations have been proposed. In this work the geometrical characteristics of a non-Newtonian shear thinning liquid, flowing in an inclined open microchannel, have been experimentally investigated and design correlations that can predict with reasonable accuracy the features of a FFMR have been proposed. The test section used was an open μ-channel with square cross section (Wo=1200 μm) made of brass which can be set to various inclination angles. The liquid film characteristics were measured by a non-intrusive technique that is based on the features of a μ-PIV system. Relevant CFD simulations revealed that the volume average dynamic viscosity over the flow domain is practically the same as the corresponding asymptotic viscosity value, which can thus be used in proposed the design equations. Finally, a generalized algorithm for the design of FFMRs, containing non-Newtonian shear thinning liquids, is suggested.

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Seeds represent the major source of food protein, impacting on both human nutrition and animal feeding. Therefore, seed quality needs to be appropriately addressed in the context of viability and food safety. Indeed, long-term and inappropriate storage of seeds might result in enhancement of protein glycation, which might affect their quality and longevity. Glycation of seed proteins can be probed by exhaustive acid hydrolysis and quantification of the glycation adduct Nɛ-(carboxymethyl)lysine (CML) by liquid chromatography-mass spectrometry (LC-MS). This approach, however, does not allow analysis of thermally and chemically labile glycation adducts, like glyoxal-, methylglyoxal- and 3-deoxyglucosone-derived hydroimidazolones. Although enzymatic hydrolysis might be a good solution in this context, it requires aqueous conditions, which cannot ensure reconstitution of seed protein isolates. Because of this, the complete profiles of seed AGEs are not characterized so far. Therefore, here we propose the approach, giving access to quantitative solubilization of seed proteins in presence of sodium dodecyl sulfate (SDS) and their quantitative enzymatic hydrolysis prior to removal of SDS by reversed phase solid phase extraction (RP-SPE). Using MG-H1 as a case example, we demonstrate the applicability of this method for reliable and sensitive LC-MS-based quantification of chemically labile AGEs and its compatibility with bioassays.

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This study was conducted to investigate the effect of supplementing different types of methionine (L and D-type) and its precursor (HMBi) on milk protein synthesis using immortalized bovine mammary epithelial cell line (MAC-T Cell); D-methionine (D-Met), L-methionine (L-met) and 2-hydroxy-4-methylthiobutanoic acid I (HMBi), an isopropyl ester of the hydroxy analogue precursor of methionine. The underlying mechanism of milk protein synthesis by adding D- and L-type amino acid as well as HMBi was elucidated through omics analysis to verify the metabolism pathway. Results showed that HMBi group showed the highest beta casein mRNA expression levels compared to D- and L-Met groups and highest medium protein although not different with the L-Met treatment. The observed upregulated (>2 protein expression vs. control) and downregulated (<0.5 protein expression vs. control) proteins in L-Met, D-Met and HMBi treated groups were: 39, 77; 46, 68; and 40, 78, respectively. Interestingly, based on protein pathway analysis, L-Met treated group stimulated the ATP synthesis, PI3 kinase and pyruvate metabolism. On the other hand, the D-Met group stimulated fructose-galactose metabolism, glycolysis pathway, PI3 kinase and pyruvate metabolism. And lastly HMBi-treated group stimulated pentose phosphate pathway and glycolysis pathway. Metabolite analysis revealed that L-Met treated group resulted in the increase in 11 metabolites. On the other hand, D-Met treated group showed increase in 7 metabolites and decreased of uridine monophosphate (UMP). HMBi supplementation caused increases of 3 metabolites and decreased of UMP and N-acetyl-L-glutamate Addition of different isoforms of Met stimulated the production of intermediate metabolites for energy production. Addition of L-Met stimulated the production of energy metabolites such as pyruvate, malate, and fumarate, well-known as intermediates of Krebs cycle. On the other hand, HMBi supplementation resulted in increases of energy metabolite glucose 1-phosphate and 6-phosphogluconate. Results showed that HMBi-treated group exhibited highest expression of β-casein mRNA expression by stimulating proteins and metabolites as well as protein and metabolic pathways involved in protein and energy synthesis. As a result, HMBi-treated group resulted in highest protein concentration but not significantly different with L-Met. Both the D- and L-isoforms has considerably the same medium protein concentration and β-casein mRNA expression higher than the control. So, D- and L-Met isoforms can be used alternatively without any significant change in protein synthesis efficiency in bovine mammary epithelial cells.

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This paper evaluates the feasibility of applying Massive MIMO to tackle the uplink mixed-service communication problem. Under the assumption of an available physical narrowband shared channel (PNSCH), devised to exclusively consume data traffic from Machine Type Communications (MTC) devices, the capacity (i:e:, number of connected devices) of MTC networks and, in turn, that of the whole system, can be increased by clustering such devices and letting each cluster share the same time-frequency physical resource blocks. Following this research line, we study the possibility of employing sub-optimal linear detectors to the problem and present a simple and practical channel estimator that works without previous knowledge of the large-scale channel coefficients. Our simulation results suggest that the proposed channel estimator performs asymptotically as well as the MMSE estimator with respect to the number of antennas and the uplink transmission power. Furthermore, the results also indicate that, as the number of antennas is made progressively larger, the performance of sub-optimal linear detection methods approaches the perfect interference-cancellation bound. The findings presented in this paper shed light on and motivate for new and exciting research lines towards a better understanding of the use of massive MIMO in MTC networks.

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In 2014, the International Union for Conservation of Nature adopted the Red List of Ecosystems (IUCN RLE) criteria as the global standard for assessing risks to terrestrial, marine, and freshwater ecosystems. Identifying and quantifying the impacts of biodiversity assessments on the status of nature is key to justifying continued investment in assessments and enabling strategic planning to maximize future impact. In this policy perspective, we use an established impact evaluation framework to identify the impacts of the IUCN RLE since its inception. To date, 1,397 ecosystem units in 100 countries have been assessed following the IUCN RLE protocol. Systematic assessments are complete or underway in more than 25 countries and two continental regions (the Americas and Europe). Countries with established ecosystem red lists have already used them to inform legislation, land-use planning, protected area expansion, monitoring and reporting, and ecosystem management. IUCN RLE indices based on systematic assessments have high potential to inform global biodiversity reporting for the Aichi Targets and the United Nations Sustainable Development Goals. Expanding the coverage of IUCN RLE assessments, building capacity to undertake them, and establishing stronger policy instruments to manage red-listed ecosystems will be key to maximizing conservation impacts over the coming decades.

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Face milling is a well known commercial process highly used in heavy industries that consumes high amount of power. Besides power issue, modern manufacturing industries are aiming for per part cost reduction keeping the product quality unimpaired. Unexpectedly if the part is rejected in any stage of manufacturing, the cost of manufacturing dramatically increases. Major cause of part rejection is excessive tool wear that imparts poor surface profile or catastrophic tool failure that causes adherence of broken tool debris onto machined surface. Furthermore, the tool wear is associated with sliding distance (frictional distance) and the tool life quantifies the cost of tools. As such, from the perspective of manufacturing industries it is imperative to optimize the surface quality parameter, cost of part, power consumption, and material removal – this is exactly what is accomplished here. By this work, it is possible to conserve power consumption, produce parts with lower cost, manufacture with uncompromising surface quality and enhanced material removal rate. Moreover, as intermediate factors of interest, the influences of sliding distance, tool life and tool flank wear on the overall machining performance are evaluated. The multi-objective optimization by Grey Relational Analysis (GRA) revealed that for improved product performance and fast manufacturing (case 1) optimum results are: feed per tooth fz = 0.25 mm/tooth, cutting speed vc = 392.6 m/min and cutting length l = 0.5 mm; for resource conservation (case 2) the optimum results are: feed per tooth fz = 0.125 mm/tooth, cutting speed vc = 392.6 m/min, cutting length l = 0.5 mm.

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Homogeneous and heterogeneous chemical reactions in partially ionized magneto-nano-liquid are investigated theoretically using finite element method (FEM). The effects of ions and electrons collisions on the transport of heat and mass are analyzed for both the cases of heterogeneous and homogeneous chemical reactions. The simultaneous effects of dispersion of nanosized particles in partially ionized nano-liquid in the presence of magnetic field are also investigated. Through numerical experiments, it is noted that the temperature of partially ionized nano-liquid increases when electrons collision rate and ion collisions are increased. The transport rate of reacting species decreases when heterogeneous and homogeneous chemical reactions strengths are increased. It is also observed that the effect of electron collisions on the flow in y-direction is the same to that of ion collisions on the flow in y-direction. Homogeneous and heterogeneous chemical reactions have similar effects on concentration of chemically reacting species in qualitative sense. However, in quantitative sense, homogeneous chemical reaction has more significant effect on the concentration reacting species as compared to heterogeneous chemical reaction.

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The black timber bark beetle Xylosandrus germanus (Blandford) is an invasive ambrosia beetle originating from Southeastern Asia that has become successfully established within Europe and North America. Herein, we provide a review of the spread and distribution of this pest of trees and timber across Europe before and after 2000, along with a review of its habitat preferences. Since the spread of X. germanus across Europe has accelerated rapidly post-2000, emphasis is placed on this period. X. germanus was first recorded in Germany in 1951 and since then in 21 European countries along with Russia. Ethanol-baited traps were deployed in oak, beech, and spruce forest ecosystems in the Western Carpathians, Central Europe, Slovakia, to characterize the distribution and habitat preference of this non-native ambrosia beetle. Captures of X. germanus within Slovakia have been rising rapidly since its first record in 2010, and now this species dominates captures of native ambrosia beetles. X. germanus has spread throughout the whole Slovakia from the south-southwest to the north-northeast over the period of 5–10 years and has also spread vertically into higher altitudes within this country. While living but weakened trees in Europe and North America are attacked by X. germanus, the greatest negative impact within Slovakia is attacks on recently felled logs of oak, beech and spruce trees providing high quality timber/lumber. We suggest that the recent rapid spread of X. germanus in Central Europe is being facilitated by environmental changes, specifically global warming, and the increasing frequency of timber trade. Recommendations for management of X. germanus in forest ecosystems are proposed and discussed, including early detection, monitoring, sanitary measures, etc.

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A series of Cu(II)-thiocyanato complexes derived from sterically hindered N-donors diamines were synthesized and characterized: catena-[Cu(Me3en)(μ-NCS)(NCS)] (1), catena-[Cu(NEt2Meen)(μ-NCS)(NCS)] (2), catena-[Cu(N,N,2,2-Me4pn)(μ-NCS)(NCS)] (3), the dimeric: [Cu2(N,N′-isp2en)2(μ-NCS)2(NCS)2] (4) and the monomeric complex [Cu(N,N′-t-Bu2en)(NCS)2] (5), where Me3en = N,N,N′-Trimethylethylenediamine, NEt2Meen = N,N-diethyl-N′-methylethylenediamine, N,N,2,2-Me4pn = N,N,2,2-tetramethylpropylenediamine, N,N′-isp2en = N,N′-diisopropylethylenediamine and N,N′-t-Bu2en = N,N′-di(tert-butyl)ethylenediamine. The complexes were characterized by elemental microanalyse, IR and UV-Vis spectroscopy and single crystal X-ray crystallography. Density Functional Theory was used to evaluate the role of steric effects in compounds 4 and 5 and how this may affect the adaption of a specific geometry, NCS-bonding mode and the dimensionality of the resulting complex.

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A pattern of NK cell heterogeneity in each individual determines proliferative and functional responses of NK cells to activating stimuli. Obtaining the progeny of a single cell by cloning original population is one of the ways to study the NK cell heterogeneity. In this work, we used single cell sorting into a plate and stimulation by IL-2 and gene-modified K562 feeder cells expressing membrane-bound IL-21 (K562-mbIL21) that led to generation of phenotypically confirmed and functionally active NK cell clones. We applied two models of clone cultivation, which differently affected their phenotype, lifespan and functional activity. The first model, which included weekly restimulation of clones with K562-mbIL21 and IL-2, resulted in the generation of relatively short-lived (5-7 weeks) clones of highly activated NK cells. HLA-DR expression in the expanded NK cells correlated strongly with IFN-γ production. The second model, in which NK cells were restimulated mainly with IL-2 alone, produced long-lived clones (8-14 weeks) that expanded up to 107 cells with lower ability to produce IFN-γ. Our method is applicable for studying variability in phenotype, proliferative and functional activity of the certain NK cell progeny in response to the stimulation, which may help in selecting NK cells best suited for clinical use.

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Pasmo (Septorialinicola) is a fungal disease causing major losses in seed yield and quality, and stem fibre quality in flax. Pasmo resistance (PR) is quantitative and has low heritability. To improve PR breeding efficiency, the accuracy of genomic prediction (GP) was evaluated using a diverse worldwide core collection of 370 accessions. Four marker sets, including three defined by 500, 134, and 67 previously identified quantitative trait loci (QTL) and one of 52,347 PR-correlated genome-wide single nucleotide polymorphisms, were used to build ridge regression best linear unbiased prediction (RR-BLUP) models using pasmo severity (PS) data collected from field experiments performed during five consecutive years. With five-fold random cross-validation, GP accuracy as high as 0.92 was obtained from the models using the 500 QTL when the average PS was used as the training dataset. GP accuracy increased with training population size, reaching values >0.9 with training population size greater than 185. Linear regression of the observed PS with the number of positive-effect QTL in accessions provided an alternative GP approach with an accuracy of 0.86. The results demonstrate the GP models based on marker information from all identified QTL and the 5-year PS average is highly effective for PR prediction.

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Background: Zika virus (ZIKV) infection has affected significantly Latin America in 2015–2017. However, most studies have been reported from Brazil and Colombia, but few of them in Central America. For these reasons we analyzed the incidence, incidence rates and evolution of cases of Honduras during 2016–2017. Methods: Using epidemiological weeks (EW) surveillance data on the ZIKV epidemics in Honduras, we estimated incidence rates (cases/100,000 population), and developed maps at national, departments and municipal levels. Results: From January 1, 2016 to December 31, 2017, a total of 32,607 cases of Zika were reported (98.5% in 2016 for an incidence rate of 36.85 cases/100,000 pop; 1% confirmed by RT-PCR). The highest peak was reached on the EW 6°, 2016 (2,559 cases; 29.34 cases/100,000 pop). The department with the highest number of cases and incidence rate was Cortés (13,128 cases, 791.08 cases/100,000 pop in 2016). Discussion: Pattern and evolution of Zika in Honduras has been like those that occurred for chikungunya in 2015, that we analyzed and previously reported, affecting predominantly the central and capital area of the country, reaching also high incidences there >750 cases/100,000 pop. Studies using geographical information systems, to map its epidemiology, as well on the clinical aspects linked to, are necessary in this country, as well for the assessment of risk for travelers who visit specific areas in a destination country.

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We propose a new technique to prepare statistically-robust benchmarking data for evaluating chemical transport model meteorology and air quality parameters within the urban boundary layer. The approach employs atmospheric class-typing, using nocturnal radon measurements to assign atmospheric mixing classes, and can be applied temporally (across the diurnal cycle), or spatially (to create angular distributions of pollutants as a top-down constraint on emissions inventories). In this study only a short (<1-month) campaign is used, but grouping of the relative mixing classes based on nocturnal mean radon concentrations can be adjusted according to dataset length (i.e., number of days per category), or desired range of within-class variability. Calculating hourly distributions of observed and simulated values across diurnal composites of each class-type helps to: (i) bridge the gap between scales of simulation and observation, (ii) represent the variability associated with spatial and temporal heterogeneity of sources and meteorology without being confused by it, and (iii) provide an objective way to group results over whole diurnal cycles that separates ‘natural complicating factors’ (synoptic non-stationarity, rainfall, mesoscale motions, extreme stability, etc.) from problems related to parameterizations, or between-model differences. We demonstrate the utility of this technique using output from a suite of seven contemporary regional forecast and chemical transport models. Meteorological model skill varied across the diurnal cycle for all models, with an additional dependence on the atmospheric mixing class that varied between models. From an air quality perspective, model skill regarding the duration and magnitude of morning and evening “rush hour” pollution events varied strongly as a function of mixing class. Model skill was typically the lowest when public exposure would have been the highest, which has important implications for assessing potential health risks in new and rapidly evolving urban regions, and also for prioritizing the areas of model improvement for future applications.

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To examine the role of RNA silencing in defense against viroid, a Dicer-like 2 and 4 (DCL2&4)—double knockdown transgenic tomato line 72E was created. The expression of endogenous DCL2 and DCL4 in line 72E decreased to about a half of the empty cassette line EC. When challenged with potato spindle tuber viroid (PSTVd), 72E allowed significantly higher level of PSTVd accumulation early in infection and showed lethal systemic necrosis. The size distribution of PSTVd-derived small RNA was significantly changed: the numbers of 21 and 22 nucleotides (nt) species in line 72E was approximately 66.7% and 5% of those in line EC, respectively. Conversely, the numbers of 24-nt species increased by 1100%. Furthermore, expression of miR398a-3p and miR398 increased 770–868% in the PSTVd-infected 72E, compared to the PSTVd-infected EC. In parallel, superoxide dismutase (SOD1) in PSTVd-infected 72E showed higher expression levels. In concert with miR398a-3p, SOD1 controls detoxification of reactive oxygen species (ROS) generated in cells. Since high levels of ROS production and its scavenging activity were observed in PSTVd-infected 72E, the lack of full-activity of DCLs was thought to have made the plant incapable to control excessive ROS production and thus resulted in to develop lethal systemic necrosis.

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Earth atmosphere is almost opaque in the infrared: about 374 W/m2 is absorbed by the atmosphere out of 396 W/m2 surface upward longwave radiation, and only about 22 W/m2 leaves the system unabsorbed in the atmospheric window. This makes rise to the idea to approximate the annual global mean energy flow system from a simple idealized greenhouse model, where the surface is surrounded by a single-layer shortwave (SW) transparent, longwave (LW) opaque, non-turbulent atmosphere. The energy flows in this geometry can be described by elementary arithmetic relationships. Starting from this model, the realistic Earth’s atmosphere can be achieved by introducing partial atmospheric SW opacity, partial atmospheric LW transparency and turbulent fluxes during the course of the deduction. The resulted global mean energy flow system is then compared to several data sets such as satellite observations from the CERES mission; estimates using direct surface observations and climate models; global energy and water cycle assessments; and independent detailed clear-sky radiative transfer computations. We find that the deduction from this idealized model approximates the real values in Earth energy budget with reasonable accuracy: the deduced fluxes and the observed ones are consistent within the acknowledged error of observations; while fundamental features of the initial geometry like special ratios and definite relationships between the fluxes are preserved.

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A simple procedure to obtain 1,5-disubstituted 1,2,3-triazoles, using the catalytic system erbium(III) triﬂuoromethanesulfonate, 1-methyl pyridinium triﬂuoromethanesulfonate and water is described. The reaction proceeds through an eliminative azide–olefin cycloaddition (EAOC) offering a highly regioselective approach and good yields (81–94%). The advantages of this method include simple operations of work-up and the ability of the catalytic system to be re-used five times without an evident loss in yield.

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Carotenoid and carotenoid esters profiles of peel, pulp and whole fruit tissues of astringent persimmon (Diospyrus kaki Thunb., var. Rojo Brillante) have been characterized in detail and quantified for the first time. Carotenoids were determined by HPLC-PDA-MS/MS (APCI+), using a reverse phase C30 column. A total of 38 carotenoids were identified and quantified, corresponding to 21 free carotenoids (13 xanthophylls and 8 hydrocarbon carotenes) and a total of 17 carotenoid esters. The qualitative profiles are very similar among tissues, differing only in the carotenoids concentration. The most important identified free xanthophylls were (all-E)-β-cryptoxanthin, (all-E)-antheraxanthin, (all-E)-lutein, (all-E)-zeaxanthin and (all-E)-violaxanthin . Hydrocarbon carotenoids found were (all-E)-β-carotene, (all-E)-α-carotene, (9Z)-β-carotene, (13Z)-β-carotene, (9Z)-α-carotene, and lycopene. The most abundant carotenoid esters were (all-E)-lutein-3-O-palmitate, (all-E)-zeaxanthin myristate, (all-E)-zeaxanthin palmitate and (all-E)-cryptoxanthin laurate. Processing by high pressures produced no regular effect on persimmon carotenoids and pasteurization affected negatively the content of all carotenoids from all studied persimmon tissues. This work will contribute to the development of scientific research about the bioaccessibity and bioavailabity of each individual free or esterified persimmon carotenoids in order to a better understanding of the carotenoid compounds impact in human health.

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The advent of the genome editing era brings forth the promise of adoptive cell transfer using engineered chimeric antigen receptor (CAR) T-cells for targeted cancer therapy. CAR T-cell immunotherapy is probably one of the most encouraging developments for the treatment of hematological malignancies. In 2017, two CAR T-cell therapies were approved by the U. S Food and Drug Administration; one for the treatment of pediatric Acute Lymphoblastic Leukemia (ALL), the other for adult patients with advanced lymphomas. However, despite significant progress in the area, CAR T-cell therapy is still in its early days and faces significant challenges, including the complexity and costs associated with the technology. B-cell lymphoma is the most common hematopoietic cancer in dogs, with an incidence approaching 0.1% and a total of 20-100 cases per 100,000 individuals. It is a widely accepted naturally occurring model for human non-Hodgkin’s lymphoma. Current treatment is with combination chemotherapy protocols, which prolong life for less than a year in canines and are associated with severe dose-limiting side effects, such as gastrointestinal and bone marrow toxicity. To date, one canine study generated CAR T-cells by transfection of mRNA for CAR domain expression. While this was shown to provide a transient anti-tumor activity, results were modest, indicating that stable, genomic integration of CAR modules is required in order to achieve lasting therapeutic benefit. This Commentary summarizes the current state of knowledge on CAR T-cell immunotherapy in human medicine and its potential applications in animal health, while discussing the potential of the canine model as a translational system for immuno-oncology research.

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A balanced chromosomal translocation disrupting DISC1 (Disrupted in Schizophrenia 1) gene has been linked to psychiatric diseases, such as major depression, bipolar disorder and schizophrenia. Since the discovery of this translocation, many studies have focused on understating the role of the truncated isoform of DISC1, hypothesizing that the gain of function of this protein could be behind the neurobiology of mental conditions, but not so many studies have focused in the mechanisms impaired due to its loss of function. For that reason, we perform an analysis on the cellular proteome of primary neurons in which DISC1 was knocked down with the goal of identifying relevant pathways directly affected by DISC1 loss of function. Using an unbiased proteomic approach, we found that the expression of 31 proteins related to neurodevelopment (e.g. CRMP-2, stathmin) and synaptic function (e.g. MUNC-18, NCS-1) is regulated by DISC1 in primary mouse neurons. Hence, this study reinforces the idea that DISC1 is a unifying regulator of both neurodevelopment and synaptic function, thereby providing a link between these two key anatomical and cellular circuitries.

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Dispersed silver nanoparticles (AgNPs) on the surface of titanium alloy (Ti6Al4V) and titanium alloy modified by titania nanotube layer (Ti6Al4V/TNT) substrates were produced by chemical vapor deposition method (CVD) using novel precursor of the formula [Ag5(O2CC2F5)5(H2O)3]. The structure and volatile properties of this compound were determined using single crystal X-ray diffractometry, variable temperature IR spectrophotometry (VT IR), and electron inducted mass spectrometry (EI MS). The morphology and the structure of the produced Ti6Al4V/AgNPs, and Ti6Al4V/TNT/AgNPs composites were characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Moreover, measurements of hardness, Young’s modulus, adhesion, and surface free energy have been carried out. The ability to release silver ions from the surface of produced nanocomposite materials immersed in PBS solution has been estimated using inductively coupled plasma mass spectrometry (ICP MS). The wettability and the surface free energy of samples were estimated on the base of contact angle studies with the use of water and diiodomethane. Among the studied surface-modified titanium alloy implants, the best nano-mechanical properties were noticed for the Ti6Al4V/TNT15/AgNPs composite. The location of silver nanoparticles inside of titania nanotubes caused their lowest release rate, which may indicate on suitable properties above mentioned type of the composite for the construction of implants with a long term of antimicrobial activity.

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Due to rapid urbanization, the quantity of wastewater treatment plants (WWTP) has increased, and with it the amount of waste generated by them. Sustainable management of this waste can lead to the creation of energy-rich biogas through the fermentation process. This review presents recent advances in the anaerobic digestion process resulting in greater biogas production. Disintegration techniques for enhancing waste activated sludge fermentation can be generally partitioned into biological, physical and chemical, each of which are covered in this review. These disintegration techniques were compared mainly in terms of their biogas yield. It was found that ultrasonic and microwave disintegration provides the highest biogas yield (>500%); however, they are also the most energy demanding (>10,000 kJ kg-1 total solids).

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Satellite altimeters have been used to monitor river and reservoir water levels, from which water storage estimates can be derived. Inland water altimetry can therefore play an important role in continental water resource management. Traditionally, satellite altimeters were designed to monitor homogeneous surfaces such as oceans or ice sheets, resulting in a poor performance over small inland water bodies due to the contribution from land contamination in the returned waveforms. The advent of synthetic aperture radar (SAR) altimetry (with its improved along-track spatial resolution) has enabled the measurement of inland water levels with a better accuracy and an increased spatial resolution. This paper presents three specialized algorithms or retrackers to retrieve water levels from SAR altimeter data over inland water bodies dedicated to minimizing land contamination from the waveforms. The performances of the proposed waveform portion selection method with three retrackers, namely, the threshold retracker, Offset Centre of Gravity (OCOG) retracker and 2-step physical-based retracker, are compared. Time series of water levels are retrieved for water bodies in the Ebro River basin (Spain). The results show good agreement with in situ measurements from the Ebro Reservoir (width is approximately 1.8 km) and Ribarroja Reservoir (width is approximately 400 m) with un-biased root-mean-square errors (RMSEs) of approximately 0.28 m and 0.16 m, respectively. The performances of all three retrackers are also compared with the European Space Agency’s ocean retracker in the Sentinel-3 Level-2 product.

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The processing of Mexican limes generates great amounts of peel as a byproduct. Lime peel is mainly rich in the flavonoid hesperidin, whose bioactivity is oriented mainly to cardiovascular diseases and cancer. The purpose of this work was to develop a green process for the extraction and purification of hesperidin from Mexican lime peel. The extraction of hesperidin was investigated on a laboratory scale by varying the solvent composition and the solid-to-solvent ratio. The best conditions (solid-to-solvent ratio of 0.33 g/mL and 60% ethanol) were used for the extraction of hesperidin in a pilot scale (Volume = 20 L). The kinetics of the extraction was studied to find the maximum hesperidin concentration at 100 min. The concentrated extract had a hesperidin content of 0.303 mg/mL. Next, a purification process using adsorption resins was assessed. Through static tests, it was determined that higher adsorption efficiencies were achieved with the EXA-118 resin and diluted extract (4:6 ratio with 10% DMSO). Finally, the adsorption of hesperidin from the diluted extract (hesperidin concentration of 0.109 mg/mL) was carried out at 25 °C in a column packed with 80 mL of EXA-118 resin. The mean recovery efficiency of hesperidin from the extract was almost 90%.

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The mineralocorticoid hormone aldosterone regulates sodium and potassium homeostasis but also adversely modulates the maladaptive process of cardiac adverse remodeling post-myocardial infarction. Through activation of its mineralocorticoid receptor (MR), a classic steroid hormone receptor/transcription factor, aldosterone promotes inflammation and fibrosis of the heart, the vasculature, and the kidneys. This is why MR antagonists reduce morbidity and mortality of heart disease patients and are part of the mainstay pharmacotherapy of advanced human heart failure. A plethora of animal studies using cell type–specific targeting of the MR gene have established the importance of MR signaling and function in cardiac myocytes, vascular endothelial and smooth muscle cells, renal cells, and macrophages. In terms of its signaling properties, the MR is distinct from nuclear receptors in that it has, in reality, two physiological hormonal agonists: not only aldosterone but also cortisol. In fact, in several tissues, including in the myocardium, cortisol is the primary hormone activating the MR. There is a considerable amount of evidence indicating that the effects of the MR in each tissue expressing it depend on tissue- and ligand-specific engagement of molecular co-regulators that either activate or suppress its transcriptional activity. Identification of these co-regulators for every ligand that interacts with the MR in the heart (and in other tissues) is of utmost importance therapeutically, since it can not only help elucidate fully the pathophysiological ramifications of the cardiac MR`s actions but also help design and develop novel better MR antagonist drugs for heart disease therapy. Among the various proteins the MR interacts with are molecules involved in cardiac G protein-coupled receptor (GPCR) signaling. This results in a significant amount of crosstalk between GPCRs and the MR, which can affect the latter`s activity dramatically in the heart and in other cardiovascular tissues. This review summarizes the current experimental evidence for this GPCR-MR crosstalk in the heart and discusses its pathophysiological implications for cardiac adverse remodeling as well as for heart disease therapy. Novel findings revealing non-conventional roles of GPCR signaling molecules, specifically of GPCR-kinase (GRK)-5, in cardiac MR regulation are also highlighted.

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Over the years, scarcity of fresh potable water has increased the demand for clean water. Meanwhile, with the advent of nanotechnology, the use of nanomaterials for photocatalytic degradation of pollutants in wastewaters has increased. Herein, a new type of nanohybrids of La and Mn co-doped bismuth ferrite (BiFeO3) nanoparticles embedded into transition metal carbide sheets (MXene) were prepared by a low-cost double solvent sol-gel method, and investigated for their photocatalytic activity. The photoluminescence results showed that pure BFO has highest electron hole recombination rate as compared to all the co-doped BFO/MXene nanohybrids. The larger surface area and higher electron-hole pair generation rate provides suitable environment for fast photo-degradation of organic molecules. The band gap of the prepared nanohybrids was tuned to 1.96 eV having largest BiFeO3 surface area (147 m2g−1) reported till date. Moreover, the BLFO/MXene and BLFMO-5/Mxene degraded the 92% organic pollutant from water in dark and remaining in light spectrum as compare to undoped BFO/Mxene due to enhancement of the surface area and electron-hole recombination rate upon doping. Therefore, these synthesized nanohybrids could be a promising candidate for photocatalytic applications in future.

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Senescence is a stable cell cycle arrest that is either tumor suppressive or tumor promoting depending on context. Epigenetic changes such as histone methylation are known to affect both induction and suppression of senescence by altering expression of genes that regulate the cell cycle and the senescence-associated secretory phenotype. A conserved group of proteins containing a Jumonji C (JmjC) domain alter chromatin state, and therefore gene expression, by demethylating histones. Here, we will discuss what is currently known about JmjC demethylases in induction of senescence and how these enzymes suppress senescence to contribute to tumorigenesis.

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The development of new target stations for radioisotope production based on a dedicated 70~MeV commercial cyclotron is described. Currently known as the South African Isotope Facility (SAIF), this initiative will free the existing separated-sector cyclotron (SSC) at iThemba LABS (near Cape Town) to mainly pursue research activities in nuclear physics and radiobiology. It is foreseen that the completed SAIF facility will realize a three-fold increase in radioisotope production capacity compared to the current programme based on the SSC.

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The study was done to determine the effect of supplementing different forms of L-methionine (L-Met) and acetate on protein synthesis in immortalized bovine mammary epithelial cell line (MAC-T Cell): Control, L-Met, conjugated L-Met and acetate (CMA), and non-conjugated L-Met and Acetate (NMA). Protein synthesis mechanism was determined by omics method. NMA group had the highest protein content in the media and β-casein mRNA expression levels (P < 0.05). The number of upregulated and downregulated proteins observed were 77 and 62 in CMA group and 50 and 81 in NMA group from 448 proteins, respectively (P < 0.05). NMA and CMA treatments stimulated pathways related to protein and energy metabolism (P < 0.05). Metabolomic analysis also revealed CMA and NMA treatments resulted in increases of several metabolites (P < 0.05). In conclusion, NMA treatment increased protein concentration and expression level of β-casein mRNA in MAC-T cells compared to CMA.

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The Landau damping effect was observed in collisionless plasma, as a microscopic resonant mechanism between electromagnetic radiation and the collective modes. In this paper we demonstrate the occurrence of the Landau damping at macroscopic scale in the interaction between water waves and anharmonic lattice of magnetic buoys. By coupling the Navier-Stokes equations for incompressible fluid with the nonlinear dynamics of an anharmonic magnetic lattice we obtain a resonant transfer of momentum and energy between the two systems. The velocity of the flow is obtained in the Stokes approximation with Basset type of drag force. The dynamics of the buoys is calculated in the surfactant approximation for a specific frequency, then we use Fourier analysis to obtain the general time variable interaction. After involving an integral Dirichlet transform we obtain the time dependent expression of the drag force, the interaction waves-lattice with a new term in the form of a Caputo fractional derivative. We compare the results of the model with experiments performed in a wave tank with free floating magnetic buoys under the action of small amplitude gravitational waves. This configuration can be applied in studies for the attenuation with resonant damping of rogue waves, storms or tsunamis.

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Three-dimensional (3D) printing technologies are transforming the design and manufacture of components and products across a variety of disciplines, however their application in the construction industry is still limited. Material deposition processes can achieve infinite geometries and have advanced from rapid prototyping and model-scale markets to their application in fabricating functional products, large objects and the construction of full-scale buildings. Many international projects have recently been realized and the construction industry is beginning to utilise these dynamic technologies. The potential advantages for integrating 3D printing into house construction are significant, these include the capacity for mass customization of designs and parameters for functional and aesthetic purposes, reduction in construction waste from highly precise material placement, and the use of recycled waste products in layer deposition materials. With the ultimate goal of improving construction efficiency and decreasing building costs, applying Strand7 Finite Element Analysis software, a numerical model was designed specifically for 3D printing in a cement mix incorporated with recycled waste product High Density Polyethylene (HDPE) and found that construction of an arched truss-like roof was structurally feasible without the need for steel reinforcements. The lab sizes prototypes were manufactured based on the destined numerical model by using a 3D printing technology. Currently available 3D printing technologies can be adopted for building construction and this paper discusses the applications, advantages, limitations and future directions of 3D printing as an innovative and viable solution for affordable house construction.

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Nowadays, the imidazolium-based ionic liquids containing acetate counter-ions are attracting much attention as both highly selective absorbents of the acidic gases and CO2 carriers in the supported ionic liquid membranes. In this regard, the investigation of the gas transport properties of such membranes may be appropriate for better understanding of various factors affecting the separation performance and the selection of the optimal operating conditions. In this work, we have tested CH4, CO2 and H2S permeability across the SILM impregnated by 1-butyl-3-methylimidazolium acetate (bmim[ace]) with the following determination of the ideal selectivity in order to compare the facilitated transport membrane performance with the SILM that dissolves acidic gases physically, namely, containing 1-butyl-3-methylimidazolium tetrafluoroborate (bmim[BF4]). Both SILMs have showed modest individual gases permeability and ideal selectivity of CO2/CH4 and H2S/CH4 separation that achieves values up to 15 and 32, respectively. The effect of the feed gas mixture composition on the permeability of acidic gases and permeselectivity of the gas pair was investigated. It turned out that the permeation behavior for the bmim[ace]-based SILM toward the binary CO2/CH4, H2S/CH4 and ternary CO2/H2S/CH4 mixtures was featured with high acidic gases selectivity due to the relatively low methane penetration through the liquid phase saturated by acidic gases.

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This paper based on systems - theoretic approach to the definition of a country's GDP as not directly observable characteristic of system state. Leontief dynamic model is generalized to take into account the stimulating effect of consumption on GDP growth. In consumption, apart from final consumption, terms are considered: balance of foreign trade, fictitious investments and hidden costs. The Kalman filter uses Rosstat's gross output (for system output) and final consumption (for system control) data from 1995 to 2015. It is concluded that if in the years 2014, 2015 it was possible to increase consumption by 5% by, say, price cuts or some increase in money supply, then GDP would be greater by about 2.5%. GDP real values in recent years are most likely greater than official values. Fictitious investments and hidden costs are found in the amount of up to third the value of final consumption. The accuracy of one-year forecasts of true GDP by the methodology of this article is approximately 1.5%.

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1) Background: The aim was to evaluate the bioefficacy of vitamin D (VitD) encapsulated in nanoemulsions developed by sonication and pH-shifting of pea protein isolate in restoring VitD status in VitD-deficient rats. 2) Methods: Weaned (3-week old), male albino rats (n = 35) were initially divided into two groups: control sufficient group (VDS; n = 7) fed on a normal AIN-93G diet and a VitD-deficient group (n = 28) fed a VitD-deficient diet for six weeks. VitD-deficient rats were divided into four subgroups: two treatment groups (Nano+VitD and Oil+VitD) and two control groups (Nano-VitD and Oil-VitD), receiving seven rats in each sub-group. Nano+VitD and Oil+VitD groups received VitD dispersed in PPI-nanoemulsions and in canola oil, respectively, while the control groups received the respective delivery vehicles without VitD. Serum 25-hydroxyvitamin D [25(OH)VitD], parathyroid hormone (PTH), calcium (Ca), phosphorus levels (P), and alkaline phosphatase (ALP) activity were measured. Femur bone was used to prepare histopathological sections. 3) Results: After one week of treatment, the VitD-deficient rats consuming Nano+VitD recovered from VitD deficiency (serum 25(OH)VitD 34.38 ± 7.00) compared to the sufficient control (36.84 ± 9.16; p > 0.05) and the deficient control consuming VitD+Oil (14.05 ± 3.08; p < 0.01). Enhancement in VitD status was followed with expected changes in serum PTH, Ca, P, and ALP levels, no difference in similar biomarkers against the sufficient control, and an improvement of the osteoid area and reduction of trabecular separation in bone. 4) Conclusions: Stabilization of VitD within PPI-based nanoemulsions enhances its absorption and restores its status and biomarkers of bone resorption in VitD-deficient rats.

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System level diagnosis is an abstraction of high level and, thus, its practical implementation to particular cases of complex systems is the task which requires additional investigations, both theoretical and modeling. Mostly, diagnosis at system level intends to identify only permanently faulty units. In the paper, we consider the case when both permanently and intermittently faulty units can occur in the system. Identification of intermittently faulty units has some specifics which we have considered in this paper. We also suggest the method which allows distinguishing among different types of intermittent faults. Diagnosis procedure was suggested for each type of intermittent faults.

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Yeasts belonging to the Metschnikowia genus are particularly interesting for the unusual formation of only two needle-shaped ascospores during their mating cycle. Presently, the meiotic process that can lead to only two spores from a diploid zygote is poorly understood. The expression of fluorescent nuclear proteins should allow the meiotic process to be visualized in vivo; however, no large-spored species of Metschnikowia has ever been transformed. Accordingly, we aimed to develop a transformation method for Metschnikowia borealis, a particularly large-spored species of Metschnikowia, with the goal of enabling the genetic manipulations required to study biological processes in detail. Genetic analyses confirmed that M. borealis, and many other Metchnikowiacea, are CUG-Ser yeasts. Codon-optimized selectable markers lacking CUG codons were used to successfully transform M. borealis by electroporation and lithium acetate, and transformants appeared to be the result of random integration. Mating experiments confirmed that transformed-strains were capable of generating large asci and undergoing recombination. Finally, random integration was used to transform an additional 18 yeast strains, and all attempts successfully generated transformants. The results provide a simple method to transform many yeasts from an array of different clades and can be used to study or develop many species for various applications.

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Over the past few decades, the growth of the urban population has been remarkable. Nowadays, 50% of the population lives in urban areas, and forecasts point that by 2050 this number will reach 70%. Today, 64% of all travel made is within urban environments and the total amount of urban kilometers traveled is expected to triple by 2050. Thus, seeking novel solutions for urban mobility becomes paramount for 21st century society. In this work, we discuss the performance of vehicular networks. We consider the metric Delta Network. The Delta Network characterizes the connectivity of the vehicular network through the percentage of travel time in which vehicles are connected to roadside units. This article reviews the concept of Delta Network and extends its study through the presentation of a general heuristic based on the definition of scores to identify the areas of the road network that should receive coverage. After defining the general heuristic, we show how small changes in the score computation can generate very distinct (and interesting) patterns of coverage, each one suited to a given scenario. In order to exemplify such behavior, we propose three deployment strategies based on simply changing the computation of scores. The results show that the strategies derived from the general heuristic are very interesting, all of them deploying roadside units in a circle pattern around the traffic epicenter.

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The diverse socio-economic and environmental impacts that the set-up of a new photovoltaic installation has must be weighed carefully in order to reach the best possible solution. Among the different photovoltaic systems there are several classification criteria, depending on the technology, application and the size of the modules that define them. The size (installed nominal capacity) stands out as an impartial and critical measure in the decision making process. In this article we use a multi-criteria decision making method to analyse the responses of five experts to a detailed questionnaire in which several different criteria are correlated with various photovoltaic installation sizes. The limitation associated to the low number of experts is addressed with a robustness and sensitivity analysis. With this study we seek first, to apply and demonstrate the feasibility of a methodology which combines technical information with multi-criteria decision making methods, and second, to obtain a clear result oriented that increases the benefits of a forthcoming photovoltaic installation of modules in distributed generation adding up to 1GW total peak power in standard conditions. We observe a consistent result in which smaller photovoltaic modules are the ideal solution that maximises the socio-economic benefits of any installation. If a decision has to be taken about the type of photovoltaic plant to be installed, the conclusion is clear: given a certain size, small, easily scalable installations are the best solution for stake-holders, for the inhabitants, and for the environment.

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We use oblate coordinates to study its resulting orbit equations. Their related solutions of Einstein's vacuum equations can be written as a linear combination of Legendre polynomials of positive denite integers $l$. Starting from solutions of the zeroth order $l=0$ in a nearly newtonian regime, we obtain a non-trivial formula favoring both retrograde and advanced solutions for the apsidal precession depending on parameters related to the metric coecients, particularly applied to the apsidal precessions of Mercury and asteroids (Icarus and 2 Pallas). As a realization of the equivalence problem in general Relativity, a comparison is made with the resulting perihelion shift produced by Weyl cylindric coordinates and the Schwarzschild solution analyzing how different geometries of space-time influence on solutions in astrophysical phenomena.

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Endo-reticular stress induces the unfolded protein response including a highly conserved set of genes crucial for cell survival against a variety of onslaughts. Among the activated stress response genes is Ire1, which undergoes auto-phosphorylation and acquires a regulated Ire1-dependent mRNA decay activity. Ire1P non-canonically splices the mRNA for Xbp1 in the cytoplasm. This spliced Xbp1 serves as mRNA encoding a transcription factor for unfolded protein response genes. Meanwhile the mRNA decay function of Ire1P degrades other cellular mRNAs and can cause changes to the translation machinery by altering regulators in a cell specific manner. Naïve splenic B cells differentiate into Antibody Secreting Cells and activate Ire1 phosphorylation early on after LPS stimulation, within 18 hrs. When Ire1 is activated in B cells, in addition to Xbp1 splicing, there are large-scale changes in mRNA; inhibition of the mRNA degradation function of Ire1 both reduces the number and changes the type of genes involved in altered splicing patterns, including factors for snRNA transcription. Some of the splicing changes seen at 18 hrs after LPS persist into the late stages of antibody secretion, up to 72 hrs, while others are supplanted by new splicing changes introduced by the induction of ELL2, a transcription elongation factor. ELL2 changes mRNA processing patterns and is necessary for Immunoglobulin secretion. RNA splicing patterns in antibody secreting cells are thus shaped by endo-reticular stress, ELL2 induction, and are associated with changes in the levels of snRNAs.

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Cost-effective and functionalized scaffolds are in high demand for stem-cell-based regenerative medicine to treat refractory bone defects in craniofacial abnormalities and injuries. One potential strategy is to utilize pharmacological and cost-effective plant polyphenols and biocompatible proteins, such as gelatin. Nevertheless, the use of chemically modified proteins with plant polyphenols in this strategy has not been standardized. Here, we demonstrated that gelatin chemically modified with epigallocatechin gallate (EGCG), the major catechin isolated from green tea, can be a useful material for dedifferentiated fat cells and adipose-derived stem cells and can induce bone regeneration in a rat congenial cleft-jaw model in vivo. Vacuum-heated gelatin sponge modified with EGCG (vhEGCG-GS) induced superior osteogenesis from these two cell types compared with vacuum-heated gelatin sponge (vhGS). The EGCG-modification converted the water wettability of vhGS to a hydrophilic property (contact angle: 110° to 3.8°) and the zeta potential to a negative surface charge; the modification enhanced the cell adhesion property and promoted calcium phosphate precipitation. These results suggest that the EGCG-modification with chemical synthesis can be a useful platform to modify the physicochemical property of gelatin. This alteration is likely to provide a preferable microenvironment for multipotent progenitor cells, inducing superior bone formation in vivo.

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In the present work a novel, portable and innovative eNose composed of a surface acoustic wave (SAW) sensor array based ZIF-8, and ZIF-67 nanocrystals (pure and combined with gold nanoparticles) as sensitive layers has been tested as a non-invasive system to detect and differentiate disease markers, such as acetone, ethanol and ammonia, related with early diagnosis of diabetes mellitus through exhaled breath. The sensors have been prepared by spin coating, achieving continuous and homogenous sensitive layers. Low concentrations (5 ppm, 10 ppm and 25ppm) of the marker analytes were measured, obtaining high sensitivities, good reproducibility, short time response and fast signal recovery.

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Pollution of sub-surface water reservoirs mainly rivers and streams through contaminated water point sources (CWPS) was studied. The objective was to formulate a discrete time delay mathematical model which describes the dynamics of reservoir pollution using mixing-problem processes that involve single species contaminants such as nitrates, phosphorous and detergents. The concentration of pollutants was expressed as a function of the inflow and outflow rates using the principle for the conservation of mass. Systems of ODEs generated from principles of mixing problems were refined into a system of DDEs so that the concentration of pollutant leaving the reservoir at time would be determined at some earlier instant, for the delay. The formulated model is a mathematical discrete time delay model which would be used to describe the dynamics of sub-surface water reservoir pollution. The results from the validation of the model were analyzed to determine how time delays in the mixing processes affect the rate of particle movement in water reservoirs.

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Inflammatory bowel diseases, which consist of chronic inflammatory conditions of the colon and the small intestine, are considered a global disease of our modern society. Recently, the interest toward the use of herbal therapies for the management of inflammatory bowel diseases has increased because of their effectiveness and favorable safety profile, compared to conventional drugs. Boswellia serrata Roxb. and Curcuma longa L. are amongst the most promising herbal drugs, however, their clinical use in inflammatory bowel diseases is limited and little is known on their mechanism of action. The aim of this work was to investigate the effects of two phytochemically characterized extracts of B. serrata and C. longa in an in vitro model of intestinal inflammation. Their impact on cytokine release and reactive oxygen species production, as well as the maintenance of the intestinal barrier function and on intestinal mucosa immune cells infiltration, has been evaluated. The extracts showed a good protective effect on the intestinal epithelium at 1 µg/ml, with TEER values increasing by approximately 1.5 fold, compared to LPS-stimulated cells. C. longa showed an anti-inflammatory mechanism of action, reducing IL-8, TNF-α and IL-6 production by approximately 30%, 25% and 40%, respectively, compared to the inflammatory stimuli. B. serrata action was linked to its antioxidant effect, with ROS production being reduced by 25%, compared to H2O2-stimulated Caco-2 cells. C. longa and B. serrata resulted to be promising agents for the management of inflammatory bowel diseases by modulating in vitro parameters which have been identified in the clinical conditions.

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Even if silicon alkoxides (especially ethylsilicates) have long been used as consolidants of weathered stone monuments, their physical properties are not ideal. In this study, an innovative procedure for the consolidation of sedimentary rocks was developed that combines the use of organometallic and alkylamine catalysts with the addition of well-defined nanoparticles exhibiting a narrow size distribution centered at ca 10 nm. As a suitable test material, the Pietra di Lecce limestone was selected because of its color and problematic physico-chemical properties, such as rather low hardness. Using the developed procedure, the mechanical and surface properties of the limestone were improved without the unwanted over-consolidation of the surface layers of the stone, and any significant deterioration in the pore size distribution, water vapor permeability or the stone’s appearance. The developed modified ethylsilicates penetrated deeper into the pore structure of the stone than the unmodified ones and increased the hardness of the treated material. The formed xerogels within the stone pores did not crack. Importantly, they did not significantly alter the natural characteristics of the stone.

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Adenosine to inosine (A-to-I) RNA editing is a highly conserved regulatory process carried out by adenosine-deaminases (ADARs) on dsRNAs. Although a considerable fraction of the transcriptome is edited, the function of most editing sites is unknown. Previous studies indicate changes in A-to-I RNA editing frequencies following exposure to several stress types. However, the overall effect of stress on the expression of ADAR targets is not fully understood. Here, we performed high-throughput RNA sequencing of wild-type and ADAR mutant C. elegans worms after heat-shock to analyze the effect of heat-shock stress on the expression pattern of genes. We found that ADAR regulation following heat-shock does not directly involve heat-shock related genes. Our analysis also revealed that lncRNAs and pseudogenes, which have a tendency for secondary RNA structures, are enriched among upregulated genes following heat-shock in ADAR mutant worms. The same group of genes is downregulated in ADAR mutant worms under permissive conditions, which is likely, considering that A-to-I editing protects endogenous dsRNA from RNA-interference (RNAi). Therefore, temperature increases may destabilize dsRNA structures and protect them from RNAi degradation, despite the lack of ADAR function. These findings shed new light on the dynamics of gene expression under heat-shock in relation to ADAR function.

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The steady streaming (SS) phenomenon is gaining increased attention in the microfluidics community, because it can generate net mass flow from the zero-mean vibration. We developed numerical simulation and experimental measurement tools to analyze this vibration induced flow, which has been challenging due to its unsteady nature. Validity of these analysis methods is confirmed by comparing the three-dimensional (3D) flow field induced around a cylindrical micropillar under circular vibration. In the numerical modeling, we directly solved the flow in the Lagrangian frame so that the substrate with a micropillar becomes stationary, and the result was converted to the Eulerian frame to compare them with the experimental results. The present approach enables to avoid the introduction of moving boundary or small perturbation approximation. The flow field obtained by the micro particle image velocimetry (PIV) measurement supported the three-dimensionality observed in the numerical results, which could be important for controlling the mass transport and manipulating particulate objects in the microfluidic systems.

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New research points to a possible link between Autism Spectrum Disorder and the gut microbiota as many autistic children have co-occurring gastrointestinal problems. This review focuses on specific alterations of gut microbiota mostly observed in autistic patients. Particularly, the mechanisms through which such alterations may trigger the production of the bacterial metabolites or leaky gut in autistic people are described. Various altered metabolite levels were observed in autistic children, many of those were of bacterial origin such as short chain fatty acids (SCFAs), indoles and lipopolysaccharides. A less integrative gut-blood-barrier is abundant in autistic individuals. This explains the leakage of bacterial metabolites into the patients triggering new body responses or altered metabolism. Some other co-occurring symptoms such as mitochondrial dysfunction, oxidative stress in the cells, altered tight junctions in the blood brain barrier and structural changes in cortex, hippocampus, amygdala and cerebellum were detected. Moreover, this paper suggests that autism is associated with an unbalanced gut microbiota (dysbiosis). Although the cause-effect relationship between autism and gut microbiota is not yet well established, consumption of specific probiotics may represent a powerful tool to re-establish gut homeostasis and promote gut health. Diagnostic and therapeutic value of new biomarkers leading to the perturbation in the phenylalanine metabolism will be discussed.

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The study investigated, in a rat model of low-level and moderate environmental exposure to cadmium (Cd; 1 or 5 mg Cd/kg diet, respectively, for 3-24 months), whether the co-administration of 0.1% extract from Aronia melanocarpa L. berries (AE) may protect against oxidative stress in the liver. The intoxication with Cd, dose- and duration-dependently, weakened the enzymatic antioxidative barrier (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase), decreased the concentrations of non-enzymatic antioxidants (reduced glutathione and total thiol groups), and increased the concentrations of oxidized glutathione, hydrogen peroxide, xanthine oxidase, and myeloperoxidase in this organ. These resulted in a decrease in the total antioxidative status (TAS), an increase in the total oxidative status (TOS), and development of oxidative stress in the liver (evaluated based on the index of oxidative stress calculated as the ratio of TOS and TAS). The administration of AE at both levels of Cd treatment significantly improved the enzymatic and non-enzymatic antioxidative barrier, decreased the concentration of pro-oxidants, and protected from the development of oxidative stress in the liver. In conclusion, consumption of aronia products may prevent Cd-induced destroying the oxidative/antioxidative balance and development of oxidative stress in the liver protecting against this organ damage.

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This study aims to determine the optimal configuration (position and operation duration) for wall mounted mechanical mixers based on the comparison of three-dimensional computational fluid dynamics (CFD) modelling results and physical data collected from the treatment plant. A three-dimensional model of anoxic zone 1, 2 and 3 of Northern Wastewater Treatment Plant (WWTP) located at Cairns Regional Council, Cairns, Queensland, Australia was developed and validated. The model was used to simulate the flow pattern of the WWTP and the simulation results are in good agreement with the physical data varying between 0% to 15% in key locations.
The anoxic zones were subject to velocities less than the desired 0.3 metres per second however results for suspended solids concentration indicate that good mixing is being achieved. Results for suspended solids concentrations suggest that the anoxic zones are towards the upper limits recommended by literature for specific power dissipation.
The duration for operation of mechanical mixers was investigated and identified that the duration could be reduced from 900 seconds down to 150 seconds. Alternative mixer positioning was also investigated and identified positioning which would increase the average flow velocity with decreased duration (150 seconds). The study identified that Council may achieve savings of $24,000 per year through optimisation of the mechanical mixers.

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People localization is a key building block in many applications. In this paper, we propose a deep learning based approach that significantly improves the localization accuracy and reduces the runtime of Wi-Fi based localization systems. Three variants of the deep learning approach are proposed, a sub-task architecture, an end-to-end architecture, and an architecture that incorporates prior knowledge. The performance of the three architectures under different conditions is evaluated and the significant improvement of the three architectures over existing approaches is demonstrated.

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The abnormal assembly of α-synuclein (α-Syn) is an initial step in the formation of Lewy bodies in the brain, which finally causes the neuronal death, being considered as a pathological hallmark in Parkinson’s disease (PD). Certain food bioactives or their metabolites at very low concentrations can trespass the blood brain barrier (BBB) that might, thereafter, act simultaneously. The aim of this work was to evaluate the inhibitory and destabilising capacities on α-Syn kinetics and the neuroprotective effects of three well-known bioactive compounds able to cross the BBB and present in foods; melatonin (MEL), protocatechuic acid (PCA) and hydroxytyrosol (HT), and their combinations. For this purpose, different in vitro techniques (Thioflavin T (ThT), Transmission Electronic Microscopy (TEM), electrophoresis and MTT assay) were used. All tested compounds and their combinations were able to abolish the toxicity induced by α-Syn. In addition, the combination of PCA (100 µM) +HT (100 µM) showed the highest inhibitory effect against α-Syn fibril formation and destabilises α-Syn fibrils (88 and 62%, respectively). This is the first time that MEL, PCA and HT prove a joint effect against α-Syn aggregation and toxicity when they are tested together.

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: The effect that the microstructure exerts on the TRIP phenomenon and on the mechanical properties in a multiphase steel was studied. Samples of an initially cold-rolled ferrite-pearlite steel underwent different intercritical annealing treatments at 750 °C until an equal fractions of austenite/ferrite was reached; the intercritical treatment was followed by isothermal bainitic treatments before cooling the samples to room temperature. Samples in the first treatment were heated directly to the intercritical temperature, whereas other samples were heated to either 900 or 1100 °C to obtain a fully homogenized, single phase austenitic microstructure prior to the conducting the intercritical treatment. The high temperature homogenization of austenite resulted in the decrease in its stability, so a considerable austenite fraction transformed into martensite by cooling to room temperature after the bainitic heat treatment. Most of the retained austenite transformed during the tensile tests, and as a consequence, the previously homogenized steels showed the highest UTS. In turn, the steel with a ferritic-pearlitic initial microstructure, exhibited higher ductility than the other steels and texture components that favor forming processes.

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1) Background: We tested whether AHR activation induces DNA damage, whether polymorphisms in genes related to risk of Non-Hodgkin lymphoma are associated with DNA damage, and whether the two conditions do interact with each other. 2) Methods: Our study population included 36 subjects, randomly selected among the population controls participating in a case-control study on lymphoma in Sardinia, Italy, who donated a blood sample. We investigated 47 single nucleotide polymorphisms (SNPs) previously reported to convey risk of lymphoma; the Dual-Glo® Luciferase Assay System to detect activation of the aryl hydrocarbon receptor (AhR) by the serum of study subjects; and the COMET Assay to detect DNA damage. 3) Results: Activation of the aryl hydrocarbon receptor did not increase DNA damage in our study population. On the other hand, the mutant allele (G) of rs1056932/BCL6 increased the occurrence of DNA damage (p = 0.045); such association was confirmed among AhR negative, but not AhR positive subjects. 4) Conclusions: We observed excess DNA damage associated with a gene polymorphism, namely rs1056932/ BCL6, previously reported in association with risk of lymphoma. No increase in DNA damage was associated with AhR activation per se, nor with the other gene polymorphisms we investigated.

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In this paper, we study the usage of machine learning models for sales time series forecasting. The effect of machine learning generalization has been considered. A stacking approach for building regression ensemble of single models has been studied. The results show that using stacking technics, we can improve the performance of predictive models for sales time series forecasting.

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Although distributed additive manufacturing can provide high returns on investment the current markup on commercial filament over base polymers limits deployment. These cost barriers can be surmounted by eliminating the entire process of fusing filament by 3-D printing products directly from polymer granules. Fused granular fabrication (FGF) (or fused particle fabrication (FPF)) is being held back in part by the accessibility of low-cost pelletizers and choppers. An open-source 3-D printable invention disclosed here provides for precise controlled pelletizing of both single thermopolymers as well as composites for 3-D printing. The system is designed, built and tested for its ability to provide high tolerance thermopolymer pellets from a number of sizes capable of being used in a FGF printer. In addition, the chopping pelletizer is tested for its ability to chop multi-materials simultaneously for color mixing and composite fabrication as well as precise fractional measuring back to filament. The US$185 open-source 3-D printable pelletizer chopper system was successfully fabricated and has a 0.5 kg/hr throughput with one motor, and 1.0 kg/hr throughput with two motors using only 0.24 kWh/kg during the chopping process. Pellets were successfully printed directly via FGF and indirectly after being converted into high-tolerance filament in a recyclebot.

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In this article the methodology for the determination of the theoretical gamma spectrum originated by applying DGNAA (delayed gamma neutron analysis activation) techniques for the elemental analysis of ash from thermal power plants is exposed. This is a study must be prior to the experimentation in order to define the parameters of the test to obtain the optimal conditions for the detection of each element present in the sample.

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The order Nymphaeales, consisting of three families with a record of eight genera, has gained significant interest from botanists probably due to its position as a basal-angiosperm. The phylogenetic relationships within the order have well been studied and resolved; however, a few controversial nodes still remain in the Nymphaeaceae including the position of the genus Nuphar. The position of the genus Nuphar and the monophyly of the Nymphaeaceae family remain uncertain. This study adds to the increasing number of completely sequenced plastid genomes of the Nymphaeales and applies large chloroplast gene data set in reconstructing the intergeneric relationships within the Nymphaeaceae. Five complete chloroplast genomes were newly generated, including a first one for the monotypic genus Euryale. Using a set of 66 protein coding genes from the chloroplast genomes of 17 taxa, the phylogenetic position of Nuphar was determined and a monophyletic Nymphaeaceae family was obtained with a convincing statistical support from both partitioned and unpartitioned data schemes. Although genomic comparative analyses revealed a high degree of synteny among the chloroplast genomes of the ancient angiosperms, key minor variations were evident particularly in the contraction/expansion of the Inverted Repeat regions and in RNA editing events. Genome structure, gene content and arrangement were highly conserved among the chloroplast genomes.

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The Hennovation project, an EU H2020 funded thematic network, aimed to explore the potential value of practice-led multi-actor innovation networks within the laying hen industry. The project proposed that husbandry solutions can be practice-led and effectively supported to achieve durable gains in sustainability and animal welfare. It encouraged a move away from the traditional model of science providing solutions for practice, towards a collaborative approach where expertise from science and practice were equally valued. During the 32-month project, the team facilitated 19 multi-actor networks in 5 countries through 6 critical steps in the innovation process: problem identification, generation of ideas, planning, small scale trials, implementation and sharing with others. The networks included farmers, processors, veterinarians, technical advisors, market representatives and scientists. The interaction between the farmers and the other network actors, including scientists, was essential for farmer innovation. New relationships emerged between the scientists and farmers, based on experimental learning and the co-production of knowledge for improving laying hen welfare. The project demonstrated that a practice-led approach can be a major stimulus for innovation with several networks generating novel ideas and testing them in their commercial context. The Hennovation innovation networks not only contributed to bridging the science-practice gap by application of existing scientific solutions in practice but more so by jointly finding new solutions. Successful multi-actor, practice-led innovation networks appeared to depend upon the following key factors: active participation from relevant actors, professional facilitation, moderate resource support and access to relevant expertise. Farmers and processors involved in the project were often very enthusiastic about the approach, committing significant time to the network’s activities. It is suggested that the agricultural research community and funding agencies should place greater value on practice-led multi-actor innovation networks alongside technology and advisor focused initiatives to improve animal welfare and embed best practices.

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This paper presents an overview of the principal structural and dynamics characteristics of reverse micelles (RMs) in order to highlight their structural flexibility and versatility, along with the possibility to modulate their parameters in a controlled-manner. The multifunctionality in a large range of different scientific fields is exemplified in two distinct directions: a theoretical model for mimicry of biological microenvironment and practical application in the field of nanotechnology and nano-based sensors. RMs represents a convenient experimental approach that limits the drawbacks of the conventionally biological studies in vitro, while the particular structure confers them the status of simplified mimics of cells by reproducing a complex supramolecular organization in an artificial system. The biological relevance of RMs is discussed in some particular cases referring to the confinement and crowding environment, molecular dynamics of water and cell membrane structure. The use of RMs in different range of applications seems to be more promising due to their structural and compositional flexibility, a high efficiency and selectivity being achieved. The advance in nanotechnology is based on developing new methods of nanomaterials synthesis and deposition. This review highlighting the advantages of using RMs in synthesis of nanoparticles with specific properties and in nano (bio)sensors design.

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Ageing wine is a commonly practice used in winemaking since the quality and sensory profile increase due to the extractable compounds coming from wood by means of barrels or chips. The quantitative and qualitative compounds from wood depend on the species, its origins and the treatments applied in cooperages. Traditionally, oak wood species are most often used in cooperage, specifically Quercus alba, Known as American oak and Q. robur and Q. petraea both known as French oak. However, although this stage is very common for red wines, its use is still restricted in the case of white wines. However, this topic is particularly interesting, since due to the sensorial benefits of wood contact, the option for ageing white wines in barrels or chips is increasingly and widely chosen by winemakers. This review compiles the novel strategies applied to white wines by means of wood contact in the last years with the aim to increase wine quality and sensorial features.

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Covalent DNA protein crosslinks (DPCs) are common lesions that block replication. We examine here the consequence of DPCs on mutagenesis involving replicational template-switch reactions in Escherichia coli. 5-azacytidine (5azaC) is a potent mutagen for template-switching, dependent on DNA cytosine methylase (Dcm), implicating the trapped Dcm-DNA covalent complex as the initiator for mutagenesis. The leading strand of replication is more mutable than the lagging strand, explained by blocks to the replicative helicase and/or fork regression. We find that template-switch mutagenesis induced by 5-azaC does not require DSB repair via RecABCD. The ability to induce the SOS response is anti-mutagenic by an unknown mechanism. Mutants in recB, but not recA, exhibit high constitutive rates of template-switching and we suggest that RecBCD-mediated DNA degradation prevents template-switching associated with fork regression. A mutation in the DnaB fork helicase also promotes high levels of template-switching. We also find that other DPC-inducers, formaldehyde (a non-specific crosslinker) and ciprofloxacin (a topoisomerase II poison) are also strong mutagens for template-switching. Induction of mutations and genetic rearrangements that occur by template-switching may constitute a previously unrecognized component of the genotoxicity and genetic instability promoted by DPCs.

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The complete structure and connectivity of the Caenorhabditis elegans nervous system was first published in 1986. The ‘mind of a worm’ was the first organism to have its nervous system to be reconstructed at the level of synapses, and represented a critical milestone considering today it remains the only organism to be mapped to that level of connection. Recently, the extrasynaptic connectome of neuropeptides and monoamines has been described. This review discusses recent technological advances used to perturb whole-organism neuronal function, such as: whole brain imaging, optogenetics, sonogenetics and mutant analysis, which have allowed for interrogations of both local and global neural circuits, leading to different behaviors. A better understanding of a whole organism requires combining experimental datasets with biophysical neuronal modelling, and behavioral quantification. Combining these approaches will provide a complete understanding of the worm nervous system and shed light into how networks function and interact with the synaptic network to modulate information processing and behavioral output.

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Subjective Cognitive Decline (SCD) is a possible earliest detectable sign of dementia, but we do not know what mental processes lead to elevated concern. We summarize the previous literature on the biomarkers and functional neuroanatomy of SCD. To extend the current most-popular theory of SCD, compensatory hyperactivition, we introduce a new model: breakdown of homeostasis in the prediction error minimization system. A cognitive prediction error is a discrepancy between an implicit cognitive predictions and the corresponding outcome. Experiencing frequent prediction errors may be a primary source of elevated subjective concern. Our homeostasis breakdown model explains the progression both from normal cognition to SCD and from SCD to advanced dementia stages.

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The ANTIATERO-ALIM study was a randomized, parallel design nutritional trial testing functional food (FF) diets against the usual diet recommended in the metabolic syndrome. Functional meals included balsamic vinegar from apples and honey and grape juice enriched with polyphenols from seeds of red grapes. 300 patients with metabolic syndrome were randomized into 4 groups: gr.1: FF + Ω-3 supplements, gr.2: FF, gr.3: Ω-3 supplements, gr.4: control. IRHOMA insulin resistance, plasma lipids and oxidative stress were assessed at inclusion and at 6 months. After 6 months there was a very significant decrease of oxidative stress in group 3, followed by a significant decrease in groups 1 and 2.

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The three heat-induced coffee contaminants acrylamide, furfuryl alcohol (FA) and 5-hydroxymethylfurfural (HMF) were analyzed in a collective of commercial samples as well as in Coffea arabica seeds roasted under controlled conditions from very light Scandinavian style to very dark Neapolitan style profiles. Regarding acrylamide, average contents in commercial samples were lower than in a previous study in 2002 (196 compared to 303 µg/kg). The roasting experiment confirmed the inverse relationship between roasting degree and acrylamide content, i.e. the lighter the coffee the higher the acrylamide content. However, FA and HMF were inversely related to acrylamide and found in higher contents in darker roasts. Therefore, mitigation measures must consider all contaminants and not be focused isolatedly on acrylamide, specifically since FA and HMF are contained in much higher contents with lower margins of exposure compared to acrylamide.

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Academic interest in social and human capital is growing significantly. Similarly, their relationship with sustainability is increasing, especially compared to sustainability’s relationship with natural capital and financial and economic capital. Bibliometric and visualization research on these relationships is nonetheless insufficient. This study analyzes the evolution of the literature on natural capital, financial and economic capital, and social and human capital related to sustainability. On the other hand, the study presents a bibliometric analysis on social capital and human capital (SHC) related to sustainability. The article studies 635 references collected from the Web of Science (WoS) Core Collection database and utilizes visualization of similarities (VOS) viewer program to graphically map the material. The analysis involves co-occurrence of keywords, co-citation, and co-authorship. The results reveal not only the state of the art and the leading trends, but also the evolution regarding impact, main journals, documents, topics, authors, institutions, and countries. The study provides researchers and practitioners with a visual and schematic frame of the research on this topic.

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The BIOTON® biochar, produced by a wood biomass pyrolysis process, usually applied as a soil amendment, was investigated for a novel application, i.e. the adsorption of lead from contaminated solutions. The experimental activity firstly included the physical-chemical characterization of BIOTON®; SEM images were also obtained to highlight its internal structure. The adsorption process was investigated through batch and column experiments. Adsorption kinetics showed a very rapid achievement of the equilibrium conditions, i.e. at 2h and 4h for 50 mg/L and 100 mg/L initial Pb concentration, respectively. Complete removal also occurred within the same time. The Brunauer–Emmett–Teller model better fitted the equilibrium data for both Pb concentrations, whereas the kinetics were best represented by the pseudo second order model. The column tests showed that the addition of biochar as adsorbent media within the bed significantly extended the time of breakthrough and exhaustion, with respect to the column filled with soil only. The adsorption capacities of BIOTON® versus lead solutions was found to be comparable to that reported for commercial adsorbents. Therefore, BIOTON® can be considered a valid option, with the additional benefit to reduce the environmental impact since allows to recover a residue which alternately would need to be disposed of.

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A paper impregnated with silver nanoparticles (AgNPs) has been prepared. For the preparation of the substrates, aqueous suspensions of pulp fines, a side product from the paper production, have been mixed with Ag nanoparticles (AgNP) suspensions. The nanoparticle synthesis thereof was carried out via laser ablation of pure Ag in water. After the sheet formation process, the leaching of the AgNPs was determined to be low while the sheets exhibited antimicrobial activity towards E. Coli.

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The segmentation and de-noising are basic operations, required in every signal processing and classification system. The classical segmentation and de-noising approaches are time-invariant. Consequently, it results in the post processing of an unnecessary information and causes an increase in the system processing activity and power consumption. In this context, an efficient event-driven segmentation and de-noising technique is proposed. It is founded on the principles of level crossing and activity selection. Therefore, it can adapt its sampling frequency, segmentation window length and position along with the filter order by analyzing the input signal local characteristics. As a result, the computational complexity and the power consumption of the proposed system is reduced compared to the counter ones. The suggested system performance is compared with the classical one. It is done for the case of a multi-channel Electroencephalogram (EEG) signals. Results show a noticeable compression gain with an effective adaptation of the de-noising filters order. It aptitudes a significant computational gain, transmission data rate reduction and power consumption reduction of the proposed technique, compared to the counter ones. It shows that the proposed solution is an attractive candidate to embed in the new generation EEG wearables.

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The aim of this paper is to develop an intelligent event-driven Electrocardiogram (ECG) processing module in order to achieve an efficient solution for diagnosis of the cardiac diseases. The suggested method acquires the signal with an event-driven A/D converter (EDADC). The output of EDADC is passed through the activity selection and interpolation blocks. It allows focusing only on the important signal parts and resampling it uniformly. Later on, the signal is de-noised. The autoregressive (AR) method is used to extract the classifiable features of the de-noised signal. Afterwards, the output is classified by employing different robust classification techniques such as support vector machines (SVMs), K- Nearest Neighbor (KNN) and Artificial Neural Network (ANN). The event-driven feature enables to adapt the system processing load according to the signal temporal variations. This interesting feature of the devised system aptitudes a drastic reduction in its processing activity and therefore in the power consumption as compared to the traditional ones. A comparison of the performance of different classifiers is also made in terms of accuracy. Results show that the proposed system is a potential candidate for an automatic diagnosis of the cardiac diseases.

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The use of mixed-state ionic beams in collision dynamics investigations is examined. Using high resolution Auger projectile spectroscopy involving He-like ($1s^2\thinspace^1\!S, 1s2s\thinspace^{3,1}\!S$) mixed-state beams, the spectrum contributions of the $1s2s\thinspace^3\!S$ metastable beam component is effectively separated and clearly identified. This is performed with a technique that exploits two independent spectrum measurements under the same collision conditions, but with ions having quite different metastable fractions, judiciously selected by varying the ion beam charge-stripping conditions. Details of the technique are presented together with characteristic examples. In collisions of 4 MeV B$^{3+}$ with H$_2$ targets, the Auger electron spectrum of the separated $1s2s\thinspace^{3}S$ boron beam component allows for a detailed analysis of the formation of the $1s2s(^3\!S)nl \thinspace^2\!L$ states by direct $nl$ transfer. In addition, the production of hollow $2s2p\thinspace^{1,3}\!P$ doubly- and $2s2p^2\thinspace^2\!D$ triply-excited states, by direct excitation and transfer-excitation processes, respectively, can also be independently studied. In similar mixed-state beam collisions of 15 MeV C$^{4+}$ with H$_2$, He, Ne and Ar targets, the contributions of the $1s^2$, $1s2s\thinspace^{3,1}S$ beam components to the formation of the $2s2p\thinspace^{3,1}\!P$ states by double-excitation, $1s\rightarrow2p$ excitation and transfer-loss processes can be clearly identified, facilitating comparisons with theoretical calculations.

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Influenza A viruses (IAV) are evolutionarily successful pathogens, capable of infecting a number of avian and mammalian species, and responsible for pandemic and seasonal epidemic disease in humans. To infect new species, IAV typically must overcome a number of species barriers to entry, replication, and egress, even while virus replication is counter-acted by antiviral host factors and innate immune mechanisms. A number of host factors have been found to regulate the replication of IAV by interacting with the viral RNA-dependent RNA polymerase (RdRP). The host factor PARP1, a poly-ADP ribosyl polymerase, was required for optimal functions of human, swine, and avian influenza RdRP in human 293T cells. In IAV infection, PARP1 was required for syntheses of viral mRNA and vRNA progeny, and for synthesis of viral nucleoprotein (NP) in human lung A549 cells. Intriguingly, pharmacological inhibition of PARP1 enzymatic activity (PARylation) by 4-amino-1,8-naphthalamide led to a 4-fold increase in RdRP activity, and a 2.3-fold increase in virus titer. Exogenous expression of the natural PARylation inhibitor PARG also enhanced RdRP activity. These data suggest a virus-host interaction dynamic where PARP1 itself is required, but cellular PARylation has a distinct suppressive modality on influenza RdRP function.

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The angiotensin-converting enzyme (ACE) is a peptidase that is involved in the synthesis of Angiotensin II, the bioactive component of the renin-angiotensin system. A growing body of literature argues for a beneficial impact of ACE inhibitors (ACEi) on age-associated metabolic disorders, mediated by cellular changes in reactive oxygen species (ROS) that improve mitochondrial function. Yet, our understanding of the relationship between ACEi therapy and metabolic parameters is limited. Here, we used three genetically diverse strains of Drosophila melanogaster to show that Lisinopril treatment reduces thoracic ROS levels and mitochondrial respiration in young flies, and increases mitochondrial content in middle-aged flies. Using untargeted metabolomics analysis, we also showed that Lisinopril perturbs the thoracic metabolic network structure by affecting metabolic pathways involved in glycogen degradation, glycolysis, and mevalonate metabolism. The Lisinopril-induced effects on mitochondrial and metabolic parameters, however, are genotype-specific and likely reflect the drug’s impact on nutrient-dependent fitness traits. Accordingly, we found that Lisinopril negatively affects survival under nutrient starvation, an effect that can be blunted by genotype and age in a manner that partially mirrors the drug-induced changes in mitochondrial respiration. In conclusion, our results provide novel and important insights into the role of ACEi in cellular metabolism.

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The present study examined differences in operant responses in adult male and female rats during distinct phases of addiction. Males and females demonstrated escalation in methamphetamine (0.05 mg/kg, i.v.) intake with females showing enhanced latency to escalate, and bingeing. Following protracted abstinence, females show reduced responses during extinction, and have greater latency to extinguish compared with males, indicating reduced craving. Females demonstrated lower context-driven reinstatement compared to males, indicating that females have less motivational significance to the context associated with methamphetamine. Whole-cell patch-clamp recordings on dentate gyrus (DG) granule cell neurons (GCNs) were performed in acute brain slices from controls and methamphetamine experienced male and female rats and neuronal excitability were evaluated from GCNs. Reinstatement of methamphetamine seeking reduced spiking in males, and increased spiking in females compared to controls, demonstrating distinct neuroadaptations in intrinsic excitability of GCNs in males and females. Reduced excitability of GCNs in males were associated with enhanced levels of neural progenitor cells, expression of plasticity-related proteins including CaMKII and choline acetyltransferase in the DG. Enhanced excitability in females were associated with increased GluN2A/2B ratio, indicating changes in postsynaptic GluN subunit composition in the DG. Altered intrinsic excitability of GCNs were associated with reduced mossy fiber terminals in the hilus and pyramidal projections, demonstrating compromised neuroplasticity in the DG in both sexes. The alterations in excitability, plasticity-related proteins and mossy fiber density were correlated with enhanced activation of microglial cells in the hilus, indicating neuroimmune responses in both sexes. Together, the present results indicate sexually dimorphic adaptive biochemical changes in excitatory neurotransmitter systems in the DG and highlight the importance of including sex as a biological variable in exploring neuroplasticity and neuroimmune changes that predict enhanced relapse to methamphetamine-seeking behaviors.

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